Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation
Open accessAbstract
Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived hormone with cellular protective actions. We hypothesized that GLP-1 would protect the endothelium from injury during inflammation. Our aims were to determine the: (1) effect of GLP-1 on basal microvascular permeability, (2) effect of GLP-1 on increased microvascular permeability induced by lipopolysaccaride (LPS), (3) involvement of the GLP-1 receptor in GLP-1 activity, and (4) involvement of the cAMP/PKA pathway in GLP-1 activity. Microvascular permeability (L(p)) of rat mesenteric post-capillary venules was measured in vivo. First, the effect of GLP-1 on basal L(p) was measured. Second, after systemic LPS injection, L(p) was measured after subsequent perfusion with GLP-1. Thirdly, L(p) was measured after LPS injection and perfusion with GLP-1+GLP-1 receptor antagonist. Lastly, L(p) was measured after LPS injection and perfusion with GLP-1+inhibitors of the cAMP/PKA pathway. Results are presented as mean area under the curve (AUC)+/-SEM. GLP-1 had no effect on L(p) (AUC: baseline=27+/-1.4, GLP-1=1+/-0.4, p=0.08). LPS increased L(p) two-fold (AUC: LPS=54+/-1.7, p<0.0001). GLP-1 reduced the LPS increase in L(p) by 75% (AUC: LPS+GLP-1=34+/-1.5, p<0.0001). GLP-1 antagonism reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+antagonist=46+/-2.0, p<0.001). The cAMP synthesis inhibitor reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+cAMP inhibitor=46+/-1.5, p<0.0001). The PKA inhibitor reduced the effects of GLP-1 by 100% (AUC: LPS+GLP-1+PKA inhibitor=56+/-1.5, p<0.0001). GLP-1 attenuates the increase in microvascular permeability induced by LPS. GLP-1 may protect the endothelium during inflammation, thus decreasing third-space fluid loss.
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GLP-1 (5.0 μM) perfusion attenuates LPS-induced microvascular permeability via the cAMP PKA pathway.
“GLP-1 (5.0 μM) perfusion attenuates LPS-induced microvascular permeability via the cAMP protein kinase A (PKA) pathway [59].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [59]
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Glucagon-like peptide-1 alleviating peripheral neuropathy in diabetic patients: advance in mechanism
Wen, X., Tang, W., & Liu, Z. (2011) · Academic Journal of Second Military Medical University · doi:10.3724/sp.j.1008.2011.00329
Iacopi, E., Riitano, N., Giangreco, F., Bellini, R., Tramonti, C., Chisari, C., & Piaggesi, A. (2026) · The International Journal of Lower Extremity Wounds · doi:10.1177/15347346261429745
- Authors
- Dozier, K. C., Cureton, E. L., Kwan, R. O., Curran, B., Sadjadi, J., & Victorino, G. P.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Victorino, Gregory P.
- Venue
- Peptides
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 30
- Issue
- 9
- Pages
- 1735-1741
- ISSN
- 0196-9781 (ISSN-L)
- PMC
- PMC2954434
- OpenAlex
- W2050489626
- Cited by
- 58
- References
- 42
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 1 · 2014: 6 · 2013: 6 · 2012: 9
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Peptides (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (K08GM081361)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- glucagon-like peptide-1, endothelial injury, inflammation, lipopolysaccharide, microvascular permeability, GLP-1 receptor, cAMP/PKA signaling, postcapillary venules, endothelial protection, PKA inhibitors, GLP-1 receptor antagonists
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Cyclic AMP, Animals, Capillary Permeability, Endothelium, Vascular, Enzyme Inhibitors, Female, Inflammation, Isoquinolines, Lipopolysaccharides, Mesentery, Peptide Fragments, Perfusion, Sulfonamides, Venules, Dideoxyadenosine, Rats, Sprague-Dawley, Cyclic AMP-Dependent Protein Kinases, Receptors, Glucagon, Rolipram, Protein Kinase Inhibitors, Rats, Glucagon-Like Peptide 1
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